The general objective of our research has been to understand the mechanisms and functional organization of the spinal pathways involved in the presynaptic control of the synaptic effectiveness of muscle, cutaneous and joint afferents and the role of these mechanisms in motor performance and sensory discrimination. One, perhaps the most attractive issue that has emerged from the studies we have performed during the last few years, is the finding of central mechanisms that produce a differential inhibition of the primary afferent depolarization (PAD) elicited in the intraspinal collaterals of individual muscle spindle afferents. This allows, at least in principle, a selective addressing of the information generated in the periphery to specific sets of neurons. One of the Specific Aims of this proposal is to analyze the extent to which the differential control of PAD observed in muscle and cutaneous afferents has any functional consequences on the postsynaptic responses elicited by these inputs in different sets of target neurons. Another, relatively unexplored aspect of the presynaptic control mechanisms, is its plasticity and adaptability in response to inflammation and peripheral nerve damage or conduction block. We now propose to study, in the anesthetized cat, the alterations in the presynaptic control of synaptic actions of joint afferents during acute inflammation of joints and skin, in view of pronounced changes in reflex actions caused by inflammatory processes, as well as the changes in the presynaptic control of transmission from cutaneous afferents following the unmasking of spinal reflexes caused by peripheral nerve damage or conduction block. We have shown recently that in the anesthetized cat there is a set spontaneously active dorsal horn neurons that modulates impulse transmission in several spinal pathways, including those mediating presynaptic inhibition of muscle and cutaneous afferents. We will now explore the functional organization of this set of neurons and some of the pathways and mechanisms that may be involved in the synchronization of their activity, and how this activity is modified by peripheral nerve damage and acute inflammation of the skin.